Recent data have shown the following: 1. Parathyroid hormone (PTH) stimulates H ion excretion in the toad bladder while having no effect on HN4 ion excretion. 2. This effect on H ion excretion by PTH appears to be mediated by cyclic-AMP and in addition, the levels of PTH used seem to be in the physiological range. 3. There is a "factor" extractable from human urine which stimultes NH4 ion excretion in the toad bladder when the subject is in an NH4Cl induced acidosis. 4. This same factor when injected into the renal artery of a dog will also produce an increased excretion of NH4 ion by the kidney while having no effect on H ion excretion (one dog). Paired hemibladders mounted between lucite chambers were used to obtain the data in items 1-3 above. One hemibladder is a control hemibladder and the other hemibladder from the same toad is the experimental hemibladder. Using these methods we are expanding the series of experiments on obtaining this factor from the urine of other human subjects and to improve the extraction procedure for obtaining the factor. We are determining if circulating PTH levels are increased in the toad in response to a metabolic acidosis and at the same time determine if the cyclic-AMP levels are increased in the mucosal cells of the toad urinary bladder during acidosis. We are also doing a correlative study on the scanning electron micrography findings compared with changes in transmission electron micrographs of the toad bladder mucosal cells, while in metabolic acidosis. Finally, we propose to determine if the factor is active in the mammalian nephron as well as the toad bladder by infusing it into the renal artery of the dog.